# Role of Skin Barrier and Immune Alterations in Allergic Sensitization

> **NIH NIH U19** · UNIVERSITY OF ROCHESTER · 2024 · $266,625

## Abstract

PROJECT SUMMARY/ABSTRACT – PROJECT 3
Atopic dermatitis (AD) often begins in the first year of life and is a precursor of allergic diseases. It is often
followed by food allergy (FA), with subsequent development of respiratory allergies. While the frequency of AD
and FA are increasing in industrialized countries, posing a large burden on healthcare, primary prevention
strategies are not yet successful. There is growing evidence that a farming lifestyle in early life in infants is
associated with a diverse microbiome and a reduced risk of atopy. We have recently shown that Old Order
Mennonites (OOM), a traditional single-family farming community, are significantly protected against early
childhood atopic disease (3.8% AD and 0% FA) as compared to a high-risk Rochester Children cohort (ROC),
born to atopic families, that show increased rates of AD (30%) and FA (15%). Consumption of unpasteurized
farm milk, exposure to farm animals, and greater microbial diversity were proposed to be associated with the
protective effects in OOM children. However, the protective mechanisms responsible for the attenuated
development of atopy in OOM children are unknown. Understanding these factors is key for development of
preventive strategies against AD and atopic conditions. Recent data suggest that epicutaneous allergen
sensitization occurs more readily through a disturbed skin barrier, as in AD. Further, development of FA is highly
associated with early, more severe AD, and skin colonization with S. aureus increases the risk to develop
FA. The effects of a farming lifestyle on promoting a healthy, homeostatic epidermal skin barrier, diverse
microbiome, and normal skin immunity, that prevent development of AD and allergic sensitization, have not
yet been evaluated. We hypothesize that lifestyle impacts the development of a healthy infant skin barrier,
immunity, and microbiome that may protect from allergic inflammation in the OOM infants or predispose towards
development of a perturbed skin barrier function and an aberrant skin immune millieu and microbiome that induce
AD and allergic sensitization in the ROC infants. We will test our hypothesis in a new longitudinal birth cohort of
high (ROC)- vs. low (OOM)-risk for development of atopy (n=80 in ROC and n=40 in OOM group), in which we
will collect lifestyle, environmental exposure, allergic sensitization, trans-epidermal-water loss/TEWL), skin tape
strips samples and skin swabs for microbiome, with the following specific aims: Specific aim 1: To determine
gene, protein, and microbiome skin biomarkers that modify the risk to develop AD or promote a healthy skin
barrier. Specific aim 2: To determine cutaneous biomarkers that promote or protect from development of FA
(and other atopic conditions), both with and without concomitant AD. Identification of the skin mechanisms,
including specific genes and pathways, and microbiome that predispose to allergic conditions, as compared to
those that may be associated with pr...

## Key facts

- **NIH application ID:** 10823362
- **Project number:** 5U19AI175113-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Emma Guttman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $266,625
- **Award type:** 5
- **Project period:** 2023-04-07 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823362

## Citation

> US National Institutes of Health, RePORTER application 10823362, Role of Skin Barrier and Immune Alterations in Allergic Sensitization (5U19AI175113-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10823362. Licensed CC0.

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